Lactobacillus johnsonii La1 attenuates Helicobacter pylori-associated gastritis and reduces levels of proinflammatory chemokines in C57BL/6 mice

In clinical settings, Lactobacillus johnsonii La1 administration has been reported to have a favorable effect on Helicobacter pylori-associated gastritis, although the mechanism remains unclear. We administered, continuously through the water supply, live La1 to H. pylori-infected C57BL/6 mice and followed colonization, the development of H. pylori-associated gastritis in the lamina propria, and the levels of proinflammatory chemokines macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived cytokine (KC) in the serum and gastric tissue over a period of 3 months. We documented a significant attenuation in both lymphocytic (P=0.038) and neutrophilic (P=0.003) inflammatory infiltration in the lamina propria as well as in the circulating levels of anti-H. pylori immunoglobulin G antibodies (P=0.003), although we did not observe a suppressive effect of La1 on H. pylori colonizing numbers. Other lactobacilli, such as L. amylovorus DCE 471 and L. acidophilus IBB 801, did not attenuate H. pylori-associated gastritis to the same extent. MIP-2 serum levels were distinctly reduced during the early stages of H. pylori infection in the La1-treated animals, as were gastric mucosal levels of MIP-2 and KC. Finally, we also observed a significant reduction (P=0.046) in H. pylori-induced interleukin-8 secretion by human adenocarcinoma AGS cells in vitro in the presence of neutralized (pH 6.8) La1 spent culture supernatants, without concomitant loss of H. pylori viability. These observations suggest that during the early infection stages, administration of La1 can attenuate H. pylori-induced gastritis in vivo, possibly by reducing proinflammatory chemotactic signals responsible for the recruitment of lymphocytes and neutrophils in the lamina propria.     

Evaluation of low dose prostaglandin E1 treatment for ductus dependent congenital heart disease

This study reports our experience with low-dose prostaglandin E₁ (PGE₁) treatment of 91 newborns with ductus dependent congenital heart disease (CHD). PGE₁ efficacy, side-effects as well as the cardiovascular and respiratory profile of the patients were analysed. PGE₁ doses > 0.02 g/kg per minute were used for only 5.3% of the total 23 656 h of treatment. The mean systolic blood pressures did not differ from the normal mean for patients with cyanotic CHD, while the diastolic values were lowered. Respiratory support was required only during 13.7% of the total treatment time. Apnoeas occurred in 21 (38%) of the 55 spontaneously breathing infants, who all had a cyanotic CHD. The incidence of apnoeas was lower during treatment with doses < 0.01 g/kg per minute.     

Ooplasmic round spermatid nuclear injection procedures as an experimental treatment for nonobstructive azoospermia

Purpose: Our objective was to apply ooplasmic round spermatid nuclear injections for the treatment of nonobstructive azoospermia. Materials: Participants were nine azoospermic men who had previously undergone diagnostic testicular biopsy. Spermatogenetic arrest was diagnosed at the round spermatid stage (n=6) or primary spermatocyte stage (n=3). A second (therapeutic) testicular biopsy was performed and round spermatid nuclei were recovered from all the participants. Results: Forty-nine mature oocytes were successfully injected with nuclei and then cultured for 72 hr. Twenty-four embryos were transferred to nine women. No pregnancy was achieved. Conclusions: Round spermatids can be recovered from therapeutic testicular biopsy material of men negative for round spermatids in previous routine diagnostic testicular biopsy specimens. Round spermatid nuclear injections may play a role in the treatment of nonobstructive azoospermia.     

Erratum to: Depression,anxiety, and quality of life in a large cohort of patients with rheumatic diseases: common,yet undertreated

Clinical Rheumatology -     

Modified CLSI Extended-Spectrum β-Lactamase (ESBL) Confirmatory Test for Phenotypic Detection of ESBLs among Enterobacteriaceae Producing Various β-Lactamases

The worldwide dissemination of Enterobacteriaceae producing AmpC β-lactamases and carbapenemases makes difficult the phenotypic detection of extended-spectrum β-lactamases (ESBLs), as they may be masked by these additional enzymes. A modification of the CLSI ESBL confirmatory test was developed and evaluated in a comparative study for its ability to successfully detect ESBLs among Enterobacteriaceae producing various carbapenemases (Klebsiella pneumoniae carbapenemase [KPC], VIM, NDM, and OXA-48) and plasmidic or derepressed AmpCs. The modified CLSI ESBL confirmatory test was performed with cefotaxime and ceftazidime disks with and without clavulanate, on which both boronic acid (BA) and EDTA were dispensed. A total of 162 genotypically confirmed ESBL-positive Enterobacteriaceae isolates (83 carbapenemase/ESBL producers, 25 AmpC/ESBL producers, and 54 ESBL-only producers) were examined. For comparison, 139 genotypically confirmed ESBL-negative Enterobacteriaceae isolates (94 of them possessed carbapenemases and 20 possessed AmpCs) were also tested. The standard CLSI ESBL confirmatory test was positive for 106 of the 162 ESBL producers (sensitivity, 65.4%) and showed false-positive results for 4 of the 139 non-ESBL producers (specificity, 97.1%). The modified CLSI ESBL confirmatory test detected 158 of 162 ESBL producers (sensitivity, 97.5%) and showed no false-positive results for non-ESBL producers (specificity, 100%). The findings of the study demonstrate that the modified CLSI ESBL confirmatory test using antibiotic disks containing both BA and EDTA accurately detects ESBLs in Enterobacteriaceae regardless of the coexistence of additional β-lactam resistance mechanisms.     

Air quality–related health damages of food

Agriculture is a major contributor to air pollution, the largest environmental risk factor for mortality in the United States and worldwide. It is largely unknown, however, how individual foods or entire diets affect human health via poor air quality. We show how food production negatively impacts human health by increasing atmospheric fine particulate matter (PM_2.5), and we identify ways to reduce these negative impacts of agriculture. We quantify the air quality–related health damages attributable to 95 agricultural commodities and 67 final food products, which encompass >99% of agricultural production in the United States. Agricultural production in the United States results in 17,900 annual air quality–related deaths, 15,900 of which are from food production. Of those, 80% are attributable to animal-based foods, both directly from animal production and indirectly from growing animal feed. On-farm interventions can reduce PM_2.5-related mortality by 50%, including improved livestock waste management and fertilizer application practices that reduce emissions of ammonia, a secondary PM_2.5 precursor, and improved crop and animal production practices that reduce primary PM_2.5 emissions from tillage, field burning, livestock dust, and machinery. Dietary shifts toward more plant-based foods that maintain protein intake and other nutritional needs could reduce agricultural air quality–related mortality by 68 to 83%. In sum, improved livestock and fertilization practices, and dietary shifts could greatly decrease the health impacts of agriculture caused by its contribution to reduced air quality.

The health and environmental consequences of feeding the increasingly large and affluent global population are becoming increasingly apparent. These consequences have spurred interest in identifying food production practices and diets that improve human health and reduce environmental harm. Recent work has demonstrated that many of the opportunities for food producers and consumers to improve nutritional outcomes also have environmental benefits, such as reducing greenhouse gas emissions, land and water use, and eutrophication (1–6). It is largely unknown, however, how individual foods and diets affect air quality, even though air pollution is the largest environmental mortality risk factor in the United States and globally (7, 8), and agriculture is itself known to be a major contributor to reduced air quality (8, 9). In the United States alone, atmospheric fine particulate matter (PM_2.5) from anthropogenic sources is responsible for about 100,000 premature deaths each year, one-fifth of which are linked to agriculture (10, 11).Here, we show how different foods affect human health by reducing air quality. We consider the emission of pollutants that contribute to atmospheric PM_2.5, the chronic exposure to which increases the incidence of premature mortality from cardiovascular disease, cancer, and stroke (12, 13). These pollutants include directly emitted PM_2.5 (primary PM_2.5) and PM_2.5 formed in the atmosphere (secondary PM_2.5) from the precursors ammonia (NH₃), nitrogen oxides (NO_x), sulfur dioxide (SO₂), and nonmethane volatile organic compounds (NMVOCs). From a spatially explicit inventory of emissions of primary PM_2.5 and secondary PM_2.5 precursors from agricultural supply chain activities for commodities in the contiguous United States (SI Appendix, Figs. S1 and S2) (14, 15) (Materials and Methods), we estimate increases in atmospheric concentrations of total (primary + secondary) PM_2.5 attributable to agricultural emissions; total PM_2.5 transport, chemistry, and removal; and exposure of populations to total PM_2.5 using an ensemble of three independent air quality models (16–19). We describe damages attributable to 95 agricultural commodities and 67 final food products (full list in SI Appendix, Table S1), which cover >99% of US agricultural production (20).     

Rapid dark aging of biomass burning as an overlooked source of oxidized organic aerosol

Oxidized organic aerosol (OOA) is a major component of ambient particulate matter, substantially impacting climate, human health, and ecosystems. OOA is readily produced in the presence of sunlight, and requires days of photooxidation to reach the levels observed in the atmosphere. High concentrations of OOA are thus expected in the summer; however, our current mechanistic understanding fails to explain elevated OOA during wintertime periods of low photochemical activity that coincide with periods of intense biomass burning. As a result, atmospheric models underpredict OOA concentrations by a factor of 3 to 5. Here we show that fresh emissions from biomass burning exposed to NO₂ and O₃ (precursors to the NO₃ radical) rapidly form OOA in the laboratory over a few hours and without any sunlight. The extent of oxidation is sensitive to relative humidity. The resulting OOA chemical composition is consistent with the observed OOA in field studies in major urban areas. Additionally, this dark chemical processing leads to significant enhancements in secondary nitrate aerosol, of which 50 to 60% is estimated to be organic. Simulations that include this understanding of dark chemical processing show that over 70% of organic aerosol from biomass burning is substantially influenced by dark oxidation. This rapid and extensive dark oxidation elevates the importance of nocturnal chemistry and biomass burning as a global source of OOA.

Highly oxidized organic aerosol (OOA) is a dominant component of particulate matter air pollution globally (1–3); however, sources of OOA remain uncertain, limiting the ability of models to accurately represent OOA and thus predict the associated climate, ecosystem, and health implications (4, 5). The current conceptual model of OOA formation suggests that anthropogenic OOA predominantly originates from the oxidation of volatile (VOCs), intermediate volatility (IVOCs), and semivolatile (SVOCs) organic compounds by the OH radical, resulting in lower-volatility products that condense to the particle phase (6). As the OH radical is formed through photolysis and has a very short atmospheric lifetime [less than a second (7)], this oxidation mechanism only occurs in the presence of sunlight. Further, the time scale for OOA formation through oxidation with OH in models is on the order of a few days (8). While this understanding is sufficient in explaining OOA concentrations in summer or periods with high solar radiation, atmospheric models fail to reproduce the observed concentration of OOA in the ambient atmosphere during winter and low-light conditions (9, 10). Fountoukis et al. (9) found simulated OOA concentrations significantly underestimated in wintertime Paris. Tsimpidi et al. (10) also reported an underprediction of simulated OOA globally in winter, suggesting missing sources of both primary OA (POA) and secondary formation pathways. This underproduction suggests a possible overlooked conversion pathway of organic vapors or particles to OOA that is not accounted for in current chemical transport and climate models.As stricter controls on fossil fuel combustion are implemented, residential biomass burning (BB) as a source of heating or cooking is becoming an increasingly important source of OA in urban environments (1, 11, 12). Further, increasing rates of wildfires from climate change are increasing the frequency of smoke-impacted days in urban areas (12–14). BB emissions include high concentrations of POA, SVOCs, IVOCs, and VOCs (15, 16), thus making BB a key source of OOA. Previous research has focused on quantifying the concentration of OOA formed through photochemical oxidation reactions (i.e., OH) with BB emissions (17, 18). However, oxidation of BB emissions in low or no sunlight is less well understood and is not included in chemical transport models. As opposed to OH, the NO₃ radical is formed through reactions with NO₂ and O₃ and is rapidly lost in the presence of sunlight (19). Thus, the NO₃ radical is only available in significant concentrations at night or other low-light conditions (20, 21). Previous research has established that biogenic VOCs may undergo oxidation at night when mixed with anthropogenic emissions containing NO₂ and O₃ (19, 22–27). There have been only a few studies that consider that nighttime oxidation of residential wood combustion may proceed through similar pathways (28–31); however, the magnitude and relevance to observed OOA in the ambient atmosphere has not yet been established. By combining laboratory experiments and ambient observations to inform a chemical transport model, we present strong evidence that nighttime oxidation of BB plumes (proceeding through reactions with O₃ and the NO₃ radical) is an important source of OOA.